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Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin.

Hajak G, Lemme K, Zisapel N - Int Clin Psychopharmacol (2015)

Bottom Line: Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal).PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each, <1%).There were no serious adverse events and no adverse events were reported after discontinuation.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Psychiatry and Psychotherapy, University of Regensburg, Regensburg bDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, Social Foundation Bamberg, Bamberg cLundbeck GmbH, Hamburg, Germany dNeurim Pharmaceuticals Ltd, Tel-Aviv, Israel eDepartment of Neurobiology Faculty of Life Sciences, Tel-Aviv University, Israel.

ABSTRACT
Surveillance studies are useful to evaluate how a new medicinal product performs in everyday treatment and how the patient who takes it feels and functions, thereby determining the benefit/risk ratio of the drug under real-life conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe for the management of primary insomnia patients age 55 years or older suffering from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine-receptor agonists), there are concerns about rebound insomnia and/or withdrawal symptoms. We report data from a postmarketing surveillance study in Germany on the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia during treatment and at early (1-2 days) and late (around 2 weeks) withdrawal. In total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7 years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the mean sleep quality (on a scale of 1-5 on which 1 is very good and 5 is very bad) improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The improvements persisted over the post-treatment observation period. Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of the patients (77%) who used traditional hypnotics before PRM treatment had stopped using them and only 5.6% of naive patients started such drugs after PRM discontinuation. PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each, <1%). There were no serious adverse events and no adverse events were reported after discontinuation. The persisting treatment effect and very low rebound rate suggest a beneficial role of sleep-wake cycle stabilization with PRM in the treatment of insomnia.

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Use of benzodiazepine and benzodiazepine-like hypnotics: number of patients who used traditional hypnotics before, during the course of, and after prolonged-release melatonin treatment. Percentage of patients using traditional hypnotics (out of 597 in the study) is also shown.
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Figure 5: Use of benzodiazepine and benzodiazepine-like hypnotics: number of patients who used traditional hypnotics before, during the course of, and after prolonged-release melatonin treatment. Percentage of patients using traditional hypnotics (out of 597 in the study) is also shown.

Mentions: Among the 597 patients in the study, 406 (68%) patients had used sleep medications before the start of Circadin 2 mg. Concomitant sleep medication other than PRM was taken by 68 (11.4%) patients during treatment and after discontinuation of PRM 138 (23.1%) patients used sleep mediations. With respect to traditional hypnotic drugs use, 276 (45.9% of the 597 patients in the study) had used benzodiazepines or benzodiazepine-like hypnotics before the start of treatment. During the PRM treatment, only 37 (6.2%) patients used traditional hypnotics and 61 (10.2%) patients used such drugs after the treatment (Fig. 5). Thus, 213 (77.7%) of the patients who had used traditional hypnotics before PRM treatment did not use them any more after discontinuation of PRM. Of the 323 patients not using benzodiazepines or benzodiazepine derivatives before the start of PRM treatment, 305 (94.4%) patients were still not using them after discontinuation of PRM and only 18 (5.6%) started using such drugs.


Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin.

Hajak G, Lemme K, Zisapel N - Int Clin Psychopharmacol (2015)

Use of benzodiazepine and benzodiazepine-like hypnotics: number of patients who used traditional hypnotics before, during the course of, and after prolonged-release melatonin treatment. Percentage of patients using traditional hypnotics (out of 597 in the study) is also shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255979&req=5

Figure 5: Use of benzodiazepine and benzodiazepine-like hypnotics: number of patients who used traditional hypnotics before, during the course of, and after prolonged-release melatonin treatment. Percentage of patients using traditional hypnotics (out of 597 in the study) is also shown.
Mentions: Among the 597 patients in the study, 406 (68%) patients had used sleep medications before the start of Circadin 2 mg. Concomitant sleep medication other than PRM was taken by 68 (11.4%) patients during treatment and after discontinuation of PRM 138 (23.1%) patients used sleep mediations. With respect to traditional hypnotic drugs use, 276 (45.9% of the 597 patients in the study) had used benzodiazepines or benzodiazepine-like hypnotics before the start of treatment. During the PRM treatment, only 37 (6.2%) patients used traditional hypnotics and 61 (10.2%) patients used such drugs after the treatment (Fig. 5). Thus, 213 (77.7%) of the patients who had used traditional hypnotics before PRM treatment did not use them any more after discontinuation of PRM. Of the 323 patients not using benzodiazepines or benzodiazepine derivatives before the start of PRM treatment, 305 (94.4%) patients were still not using them after discontinuation of PRM and only 18 (5.6%) started using such drugs.

Bottom Line: Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal).PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each, <1%).There were no serious adverse events and no adverse events were reported after discontinuation.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Psychiatry and Psychotherapy, University of Regensburg, Regensburg bDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, Social Foundation Bamberg, Bamberg cLundbeck GmbH, Hamburg, Germany dNeurim Pharmaceuticals Ltd, Tel-Aviv, Israel eDepartment of Neurobiology Faculty of Life Sciences, Tel-Aviv University, Israel.

ABSTRACT
Surveillance studies are useful to evaluate how a new medicinal product performs in everyday treatment and how the patient who takes it feels and functions, thereby determining the benefit/risk ratio of the drug under real-life conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe for the management of primary insomnia patients age 55 years or older suffering from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine-receptor agonists), there are concerns about rebound insomnia and/or withdrawal symptoms. We report data from a postmarketing surveillance study in Germany on the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia during treatment and at early (1-2 days) and late (around 2 weeks) withdrawal. In total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7 years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the mean sleep quality (on a scale of 1-5 on which 1 is very good and 5 is very bad) improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The improvements persisted over the post-treatment observation period. Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of the patients (77%) who used traditional hypnotics before PRM treatment had stopped using them and only 5.6% of naive patients started such drugs after PRM discontinuation. PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each, <1%). There were no serious adverse events and no adverse events were reported after discontinuation. The persisting treatment effect and very low rebound rate suggest a beneficial role of sleep-wake cycle stabilization with PRM in the treatment of insomnia.

Show MeSH
Related in: MedlinePlus